The increase of drug-resistant pathogens caused by the extensive use of traditional antibiotics is a serious concern worldwide. There is an urgent need to develop more effective treatment to overcome the drug-resistance problem. Antimicrobial peptides (AMP) are a new class of antibiotics with a new mode of action and remarkable therapeutic effects. In general, they contain 10-50 amino acids, with an overall positive charge and an amphipathic structure. It is well known that most AMPs can directly bind to bacteria membrane and kill them by disrupting membrane or targeting intracellular components. Most importantly, they are effective to antibiotics-resistant pathogens. This unique feature has encouraged the development of AMPs as novel antibiotics in the last few decades.
Prior to the present invention, no literature has reported that peptides derived from hepatitis B virus core protein (HBc) possess antimicrobial activities. Hepatitis B virus core protein (21 KDa) is essential for viral replication. It contains a capsid assembly domain at N-terminus (residue 1 to 149) and an arginine-rich domain (ARD) at C-terminus (residues 150 to 183) (Birnbaum et al. (1990) J. Virol 64: 3319-3330; Nassal M (1992) Virol 66: 4107-4116). ARD contains 16 arginines separated into four arginine-rich clusters (ARD I, II, IV) and has a function of binding to nucleic acids. When it binds to HBV pre-genomic RNA or palyanions, HBc can assemble into a stable capsid. In addition, ARD contains important signals for nuclear export and import of HBc core protein and particles. It was unexpectedly discovered that the growth of E. coli expressing HBc1-183 was much slower than that of E. coli expressing HBc1-149 (unpublished results).